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Neurobehavioral dysregulation, depressive symptoms, and cognition in former American football players

Year: 2026

Type: article

Abstract: Neurobehavioral dysregulation (NBD) is a core clinical feature of traumatic encephalopathy syndrome (TES), but its relationships with repetitive head impact (RHI) exposure, cognitive performance, and depressive symptoms remain unclear. This study examined clinical factors associated with NBD among former American football players with substantial RHI exposure. Cross-sectional baseline data were analyzed from 179 former American football players enrolled in the DIAGNOSE CTE Research Project, including 119 former professional and 60 former college players. NBD was assessed using measures of impulsivity, behavioral regulation, hostility, and emotional lability. Multivariate regression models evaluated associations of continuous NBD scores with depressive symptom dimensions, cognitive performance, playing level, and years of football participation, adjusting for demographic and clinical covariates. Secondary analyses evaluated dichotomized NBD outcomes using study-specific thresholds. Bonferroni-adjusted p -values were reported for multiple comparisons. Depressive symptoms demonstrated the most consistent associations with NBD. Greater neurovegetative depressive symptom burden was associated with greater impulsivity (estimate = 6.84; 95% CI = 4.45, 9.23; p -value < 0.0001), behavioral dysregulation (estimate = 11.63; 95% CI = 8.50, 14.76; p -value < 0.0001), hostility (estimate = 5.07; 95% CI = 2.32, 7.81; p -value = 0.0004), and emotional lability (estimate = 1.16; 95% CI = 0.12, 2.20; p -value = 0.0284). Greater agitated/reactive depressive symptom burden was associated with greater impulsivity (estimate = 3.42; 95% CI = 1.44, 5.41; p -value = 0.0008) and hostility (estimate = 5.11; 95% CI = 2.89, 7.32; p -value < 0.0001), while greater affective depressive symptom burden was associated with greater behavioral dysregulation (estimate = 3.09; 95% CI = 0.01, 6.18; p -value = 0.0494). Better verbal memory was associated with lower impulsivity (estimate = −2.02; 95% CI = -3.65, −0.40; p -value = 0.0149) and behavioral dysregulation (estimate = −2.64; 95% CI = −4.76, −0.52; p -value = 0.0150), while better executive speed was associated with lower behavioral dysregulation (estimate = −3.10; 95% CI = −5.11, −1.09; p -value = 0.0027). Years of football exposure was not independently associated with NBD outcomes. Among former American football players with substantial RHI exposure, depressive symptom burden was more consistently associated with NBD than football participation characteristics or cognitive performance. These findings support a heterogeneous clinical phenotype and underscore the importance of evaluating depressive symptoms when interpreting NBD in the context of TES.

Source: Frontiers in Neurology

DOI: 10.3389/fneur.2026.1952836